N-[4-[6-tert-butyl-5-methoxy-8-(6-methyl-2-oxo-1H-pyridin-3-yl)-3-quinolyl]butyl]methanesulfonamide | 1257833-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[4-[6-tert-butyl-5-methoxy-8-(6-methyl-2-oxo-1H-pyridin-3-yl)-3-quinolyl]butyl]methanesulfonamide
• 英文别名: N-{4-[6-tert-Butyl-5-methoxy-8-(6-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-quinolin-3-yl]-butyl}-methanesulfonamide；N-[4-[6-tert-butyl-5-methoxy-8-(6-methyl-2-oxo-1H-pyridin-3-yl)quinolin-3-yl]butyl]methanesulfonamide
• CAS: 1257833-46-7
• 化学式: C₂₅H₃₃N₃O₄S
• 分子量: 471.621
• InChiKey: PPENWIJYSAHVNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl N-but-3-ynyl-N-methylsulfonylcarbamate 在 copper(l) iodide 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~90.0 ℃ 、344.75 kPa 条件下， 反应 110.0h， 生成 N-[4-[6-tert-butyl-5-methoxy-8-(6-methyl-2-oxo-1H-pyridin-3-yl)-3-quinolyl]butyl]methanesulfonamide
  参考文献：
  名称：

  Discovery of N-[4-[6-tert-Butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a Potent Inhibitor of the Hepatitis C Virus NS5B Polymerase

  摘要：

  In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV. In continuation of our exploration to improve the stilbene series, the 3,5,6,8-tetrasubstituted quinoline core was identified as replacement of the stilbene moiety. 6-Methoxy-2(1H)-pyridone was identified among several heterocyclic headgroups to have the best potency. Solubility of the template was improved by replacing a planar aryl linker with a saturated pyrrolidine. Profiling of the most promising compounds led to the identification of quinoline 41 (RG7109), which was selected for advancement to clinical development.

  DOI：

  10.1021/jm401329s

文献信息

• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：de Vicente Fidalgo Javier

  公开号：US20100311760A1

  公开（公告）日：2010-12-09

  Compounds having the formula I wherein wherein R 1 , R 2 , R 3 , R 4 , X 1 , X 2 , X 3 and X 4 and as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

  具有化学式I的化合物，其中R1、R2、R3、R4、X1、X2、X3和X4如本文所定义，是丙型肝炎病毒NS5b聚合酶抑制剂。还公开了治疗HCV感染和抑制HCV复制的组合物和方法。
• US8026253B2
  申请人：——

  公开号：US8026253B2

  公开（公告）日：2011-09-27
• US8487103B2
  申请人：——

  公开号：US8487103B2

  公开（公告）日：2013-07-16
• [EN] HETEROCYCLIC ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX HÉTÉROCYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010142656A1

  公开（公告）日：2010-12-16

  Compounds having the formula (I) wherein wherein R1, R2, R3, R4, X1, X2, X3 and X4 and as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.
• Discovery of <i>N</i>-[4-[6-<i>tert</i>-Butyl-5-methoxy-8-(6-methoxy-2-oxo-1<i>H</i>-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a Potent Inhibitor of the Hepatitis C Virus NS5B Polymerase
  作者：Francisco X. Talamas、Sarah C. Abbot、Shalini Anand、Ken A. Brameld、David S. Carter、Jun Chen、Dana Davis、Javier de Vicente、Amy D. Fung、Leyi Gong、Seth F. Harris、Petra Inbar、Sharada S. Labadie、Eun K. Lee、Remy Lemoine、Sophie Le Pogam、Vincent Leveque、Jim Li、Joel McIntosh、Isabel Nájera、Jaehyeon Park、Aruna Railkar、Sonal Rajyaguru、Michael Sangi、Ryan C. Schoenfeld、Leanna R. Staben、Yunchou Tan、Joshua P. Taygerly、Armando G. Villaseñor、Paul E. Weller

  DOI：10.1021/jm401329s

  日期：2014.3.13

  In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV. In continuation of our exploration to improve the stilbene series, the 3,5,6,8-tetrasubstituted quinoline core was identified as replacement of the stilbene moiety. 6-Methoxy-2(1H)-pyridone was identified among several heterocyclic headgroups to have the best potency. Solubility of the template was improved by replacing a planar aryl linker with a saturated pyrrolidine. Profiling of the most promising compounds led to the identification of quinoline 41 (RG7109), which was selected for advancement to clinical development.